The Hovenia plant, and its herbal extract form, has been used as anti-alcohol intoxication treatment to alleviate the symptoms of hangover and other over-drinking, binge-drinking related ailments. It can reduce the alcohol concentration in the blood by enhancing the alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALHD) activities as well as promoting the protection of liver functions against free radicals.
Studies have shown that the major effective compound of Hovenia extracts is dihydromyricetin (DHM), which can promote EtOH elimination via enhancement of alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) activity. Recent study showed that at cellular level, DHM antagonized both acute EtOH-induced potentiation of GABAARs and EtOH exposure/withdrawal-induced GABAAR plasticity.
In addition to counteracting alcohol intoxication and hepatoprotective property, DHM also possess other properties such as anti-cancer, decreasing blood sugar, anti-inflammation and anti-oxidative.
Despite its therapeutic power, DHM has low water solubility and thus it is not convenient for easy administration of DHM to people in need of immediate anti-intoxication treatment, as well as other ailments that would benefit from the application of DHM, due to its lack of easy water solubility nature.
To overcome the water-solubility issue, present invention synthesized a new class of water-soluble ammonium 2,3-dihydroxy-5-((2R,3R)-3,5,7-trihydroxy-4-oxochroman-2-yl) phenolates; these compounds are named triethylammonium 2,3-dihydroxy-5-((2R,3R)-3,5,7-trihydroxy-4-oxochroman-2-yl)phenolate (TDHM) and piperidinium 2,3-dihydroxy-5-((2R,3R)-3,5,7-trihydroxy-4-oxochroman-2-yl)phenolate (PDHM) respectively, and are proved to have high water solubility and thus are suitable for immediate application and treatment to intoxicated patients.
These compounds were identified by Proton nuclear magnetic resonance and Mass spectroscopy. The PDHM solubility in water reached 5000 mg/L and that of TDHM reached 6500 mg/L.
Compared to the precursor dihydromyricetin (DHM), where the water solubility is no more than 263.54 mg/L, the TDHM and PDHM exhibited an excellent solubility.
The LD50 and MTD of PDHM are 901.57 mg/kg and 3750 mg/kg, respectively; the data figures of TDHM are 748.69 mg/kg and 748.69 mg/kg, respectively. No degeneration and necrosis pathology changes were found in livers, kidneys, hearts and lungs of the mice used in the experiments.
The results indicated that PDHM and TDHM had no significant effect on dietary and body weight in mice. Comparing with control group treated with saline, the results indicated that PDHM and TDHM could significantly decrease the blood alcohol concentration in mice by using a model of the introgastric administration of PDHM and TDHM with 2.0 mg/kg body weight.
Table 1 shows the mortality rate of mice by groups with varied concentration of TDHM.
Table 2 shows average body weight of mice changes by day on variety of concentration of TDHM
Table 3 shows dietary changes by day on variety of TDHM concentration.
Table 4 shows dietary change by day at MTD (Maximum Tolerance Dosage) of TDHM.
Table 5 shows average body weight of mice changes by day at MDT of TDHM.
Table 6 shows the mortality rate by groups with varied concentration of PDHM.
Table 7 shows average body weight of mice changes by day on variety of concentration of PDHM.
Table 8 shows dietary changes by day on variety of PDHM concentration.
Table 9 shows dietary change by day at MTD of PDHM.
Table 10 shows average body weight of mice changes by day at MDT of PDHM.
Table 11 shows the relative de-intoxication effect of DHM, TDHM and PDHM.
Table 12 shows the relative anti-alcoholism effect of DHM, TDHM and PDHM.
Table 13 shows the climbing tests result, in groups administered by DHM, TDHM and PDHM, respectively.
Table 14 shows the Dose-Effect relationship of anti-alcoholism and climbing ability of TDHM.